Dataset Information

Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia: A Randomized Double-Blind Study.

ABSTRACT:

Purpose

The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low-dose radiation therapy (LDRT) in this patient cohort.

Methods and materials

Patients admitted to the intensive care unit and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and intensive care unit clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days at day 15 postintervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers.

Results

Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day ventilator-free days was observed between groups (P = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95% confidence interval, 40.7%-99.5%) in both arms (P = .69). Apart from a more pronounced reduction in lymphocyte counts after LDRT (P < .01), analyses of secondary endpoints revealed no significant differences between the groups.

Conclusions

Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

SUBMITTER: Papachristofilou A

PROVIDER: S-EPMC7932873 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia: A Randomized Double-Blind Study.

Papachristofilou Alexandros A Finazzi Tobias T Blum Andrea A Zehnder Tatjana T Zellweger Núria N Lustenberger Jens J Bauer Tristan T Dott Christian C Avcu Yasar Y Kohler Götz G Zimmermann Frank F Pargger Hans H Siegemund Martin M

International journal of radiation oncology, biology, physics 20210305 5

<h4>Purpose</h4>The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low-dose radiation therapy (LDRT) in this patient cohort.<h4>Methods and materials</h4>Patients admitted to the intensive care unit and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiati ...[more]

PMID: 33677049

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Project description:Purpose/Objective(s) The mortality of the SARS-CoV-2 virus (COVID-19) has been associated with a pulmonary inflammatory response resulting in hypoxemia and rapid clinical decline. Recent work has indicated a potential therapeutic window for treatment to prevent ventilator-dependence thereby reducing mortality. PREVENT is an ongoing prospective multicenter Phase II randomized controlled trial where patients hospitalized with COVID-19 pneumonia are randomized to ultra-low dose radiation therapy (RT) versus control. This study is registered at clinicaltrials.gov, NCT04466683. The following is a description of the inpatient onboarding process of the center contributing the largest number of patients to this trial. Materials/Methods COVID-19 hospital admissions from the previous day were attained by the clinical research manager each morning, screened for eligibility, and then sent to the designated radiation oncologist who further delineated from this list. Common exclusion criteria were: 1. Oxygen saturation > 96% on room air, 2. Age < 50, 3. > 9 days from initial COVID-19 symptomatology. From this list, HIPAA-compliant text message contact was made with infectious disease, critical care, and nursing staff with reciprocal discussion of the trial protocol and approval for consulting the patient. Subsequently, a virtual consult was made with the patient, with witnessed informed consent obtained via telephone and in person by our research associate. Patients randomized to RT were treated within 24 hours of consent. Simulation and treatment were performed on a linear accelerator with one personal protective equipment-protected therapist moving in and out of the treatment room, and a second therapist manning the console. On-site dose calculation was performed by physics, after which the radiation oncologist approved the fields prior to treatment delivery. Simulation and treatment were performed without a computer plan; therapists underwent several practice sessions prior to treating patients on trial. Results Between August 28, 2020 and October 6, 2020, the first 10 enrolled patients on this multicenter trial were randomized and treated at our institution; no research staff member nor radiation oncology clinical team member contracted COVID-19 while employing this protocol. Conclusion This represents the first published protocol to address efficient and safe recruitment of COVID-19 patients for a radiation oncology trial. Despite the procedural hurdles of conducting a trial in the midst of a pandemic, the combination of recruitment efficiency (> 2 patients/week) and safety to the research and clinical teams (no COVID-19 infections) of this protocol has allowed for the PREVENT trial to make substantial progress in meeting recruitment goals (n = 100). This onboarding process serves as a model in conducting recruitment of COVID-19 patients for clinical trials, and is worthy of emulation at additional centers.

Project description:Pneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015.Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda.In this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ? 12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5°C. The difference in case fatality was expressed by the risk ratio between the two groups.Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).Among 127 HIV uninfected children receiving the placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children (ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100); P-value for homogeneity of risk differences = 0.006.Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However, zinc supplementation in these children significantly decreased case fatality.The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapynaïve HIV infected children in our environment.clinicaltrials.gov NCT00373100.

Project description:PurposeLow-dose radiation therapy (LD-RT) has been shown to have an anti-inflammatory effect, and preliminary results suggest it is feasible to treat patients with coronavirus disease 2019 (COVID-19) pneumonia.Materials and methodsWe conducted a prospective, single-arm, phase 1/2 clinical trial enrolling patients aged ≥50 years, who were coronavirus disease 2019 (COVID-19) positive, at phase 2 or 3 with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Primary outcome was radiologic response using severity and extension score on baseline computed tomography (CT), at days 3 and 7 after LD-RT. Secondary outcomes were toxicity using Common Terminology Criteria for Adverse Events v.5.0, duration of hospitalization, blood work evolution, and oxygen requirements using SatO2/FiO2 index (SAFI), at days 3 and 7 after LD-RT.ResultsNine patients were included. Median age was 66 (interquartile range, 57-77). Severity score was stable or decreased in the third CT but was not statistically significant (P = .28); however, there were statistically significant changes in the extension score (P = .03). SAFI index significantly improved 72 hours and 1 week after LD-RT (P = .01). Inflammatory blood parameters decreased 1 week after RT compared with baseline; only lactate dehydrogenase decreased significantly (P = .04). Two patients presented grade 2 lymphopenia after RT and another (with baseline grade 3) worsened to grade 4. Overall, the median number of days of hospitalization was 59 (range, 26-151). After RT the median number of days in the hospital was 13 (range, 4-77). With a median follow-up after RT of 112 days (range, 105-150), 7 patients were discharged and 2 patients died, 1 due to sepsis and the other with severe baseline chronic obstructive pulmonary disease from COVID-19 pneumonia.ConclusionsOur preliminary results show that LD-RT was a feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.

Dataset Information

Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia: A Randomized Double-Blind Study.

Purpose

Methods and materials

Results

Conclusions

Publications

Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia: A Randomized Double-Blind Study.

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